1. Field of the Invention
This invention relates to industrial scale preservation of sensitive biological materials. More particularly, the invention relates to technological processes and equipment for effecting the industrial scale dehydration of solutions and suspensions by foam formation, additionally providing a method for inducing bubble nucleation by mixing, chamber rotation, crystals, and ultrasound.
2. Description of the Related Art
The preservation and storage of solutions or suspensions of biologically active materials, viruses, cells and small multicellular specimens is important for food and microbiological industries, agriculture, medical and research purposes. Storage of these dehydrated biologically active materials carries enormous benefits, such as reduced weight and reduced storage space, and increased stability.
Suggestions in the prior art for providing preservation of sensitive biological materials in dehydrated form include freeze-drying and vacuum or air-desiccation. Both, freeze-drying and desiccation preservation methods have positive and negative characteristics. While freeze-drying methods are scaleable to industrial quantities, conventional vacuum and air-desiccation methods do not yield preparations of biological materials which are scalable to industrial quantities. Freezing and other steps of the freeze-drying process are very damaging to many sensitive biological materials. The freeze-drying process is very long, cost ineffective, and cannot be performed using barrier technology to insure sterility of the material.
Some of the problems associated with preservation by freezing and drying have been addressed by addition of protectant molecules, especially carbohydrates, which have been found to stabilize biological materials against the stresses of freezing and drying. However, despite the presence of protectants, the long-term stability after freeze-drying may still require low temperature storage, in order to inhibit diffusion-dependent destructive chemical reactions. Thus, further innovations have been sought to provide long-term storage of labile biological materials at ambient temperatures.
Storage of dried materials at ambient temperatures would be cost effective when compared to low temperature storage options. Furthermore, ambient temperature storage of biological materials such as vaccines and hormones would be extremely valuable in bringing modem medical treatments to third world countries where refrigeration is often unavailable. As the many benefits of shelf preservation of biological specimens have come to be appreciated, researchers have endeavored to harness vitrification as a means of protecting biological materials against degradative processes during long-term storage.
Unfortunately, the advantages of vitrification technology as a means of conferring long-term stability to labile biological materials at ambient temperatures has not been fully utilized. Conventional methods of ambient temperature preservation by desiccation are designed for laboratory processing of very small quantities of materials. Recently, Bronshtein developed an alternative method of preservation by foam formation (U.S. Pat. No. 5,766,520) that is compatible with large-scale commercial operations. Preservation by foam formation overcomes the technical problems related to scaling up desiccation and vitrification preservation processes. For this reason, preservation by foam formation is attractive as a scalable method for long-term storage of biological materials.
While foam formation is useful as a method for long-term storage of biological materials, several logistical problems remain to be solved. For example, during foam formation a large temperature gradient, up to 20 C., often persists throughout the drying chamber.
Large temperature gradients can lead to a number of technical problems including damage of sensitive biological material and increased processing time. Sensitive biological material can be damaged or destroyed in sections of the chamber where temperature is too high. Additionally, processing time is increased due to inconsistent temperature throughout the drying chamber. Furthermore, violent boiling can occur during foam formation resulting in material being carried up the chamber and thus, coating the chamber walls. Biological material splattered on chamber walls is prone to damage and, therefore lessens recovery of the sensitive material. For these reasons, an alternative method of drying sensitive biological materials by foam formation that prevents violent boiling and provides a uniformly dry, viable product would be beneficial.
The present invention addresses instrumentation problems related to preservation by foam formation and processing operations. Specially designed devices and instruments must be employed to reproducibly produce a dehydrated, shelf-stable, foams and uniform powder of the preserved materials.